The present invention is directed to a method of cancer therapy by administering (i) a pharmaceutical composition containing a compound of formula 
and (ii) a pharmaceutical composition containing paclitaxel (commercially available as Taxol(trademark)). The invention is also directed to a kit containing both of the above compositions.
The compounds of formula I below are known to be cell cycle inhibitors having potent anticancer therapeutic activity, in particular in solid tumors such as breast and colon cancers. See, e.g. U.S. Pat. Nos. 5,057,614 and 6,048,887.
Paclitaxel is also known to be useful in cancer therapeutics. See, e.g., U.S. Pat. Nos. 5,641,803 and 5,670,537 (and the references cited therein).
It has now been discovered that compounds of formula I are especially effective in cancer therapy when administered in combination with paclitaxel.
The present invention relates to a method of treating a patient suffering with cancer comprising administering to the patient, either concomitantly or sequentially, a first component consisting of a pharmaceutical composition containing as an active ingredient a compound of formula I or a pharmaceutically acceptable salt or ester of said compound and a second component consisting of a pharmaceutical composition containing paclitaxel, the amount of each component being such that the combination of components is therapeutically effective.
This combination of chemotherapeutic compounds is particularly useful in the treatment of breast, colon, rectal, lung, uterine and prostate cancers.
It was unexpectedly found that administration of the two components in accordance with the present invention results in improved antineoplastic effects that are significantly superior to the results obtained with each compound alone. Namely, administration of the two components in accordance with the present invention resulted in an improved therapeutic index (that is, superior efficacy) in comparison to either component alone without a significant increase in toxicity. Alternatively the invention permits reduction of the amount of at least one component (in comparison the amount typically given in monotherapy) while retaining a desirable therapeutic index. In preferred embodiments, the amount of both components (in comparison the amount typically given in monotherapy) is reduced affording reduced toxicity while still retaining a desirable therapeutic index.
The above findings were unexpected inasmuch as similarly designed in vitro studies using compounds of formula I in combination with other antineoplastic agents (such as gemcitabine, 5-FU and carboplatin) did not produce the magnitude of effect observed with compounds of formula I in combination with paclitaxel.
In another aspect, the invention relates to a kit. The kit comprises a first component and a second component. The first component contains one or more oral unit dosage forms of an active ingredient selected from a compound of formula I or a pharmaceutically acceptable salt or ester of said compound. The second component contains one or more injectable unit dosage forms of paclitaxel.